Physical Chemistry Seminar: Professor Stefan Stoll, University of Washington

"Quantifying protein conformations using DEER/EPR spectroscopy"

About the Seminar:

For many proteins, flexibility and motion form the basis of their function. In our lab, we quantify the conformational landscapes of proteins and their changes upon interaction with ligands and other proteins. We use Double Electron-Electron Resonance (DEER) spectroscopy, a form of Electron Paramagnetic Resonance (EPR) spectroscopy. Using DEER, we directly measure absolute distances and distance distributions within proteins. From the data, we build quantitative structural models of the protein's intrinsic flexibility, conformational substates, and the structural changes induced by ligands and binding partners. In this presentation, we summarize recent results on HCN, a hyperpolarization-activated ion channel involved in the regulation of the heartbeat. Its activity is modulated by the binding of cyclic nucleotides. The structural mechanism of this modulation is unknown. We present a DEER-based model for the conformational transition induced by ligand binding, as well as DEER-based insight into the conformational energetics. In addition, we present results on the topology of the complex between HCN and TRIP8b, a structurally uncharacterized accessory protein.

About the Speaker:

Prof. Stoll was born in Italy and received his undergraduate degrees in Chemical Engineering and in Performing Arts from universities in Graz, Austria. After a stint as a freelance musician in Vienna, he did his graduate work in Chemical Physics at the ETH Zurich in Switzerland, where he worked on theoretical spin dynamics with Arthur Schweiger. He received his PhD degree in 2003 and then continued as a postdoc at ETH Zurich, with some work at the Weizmann Institute of Science. In 2007, he moved to UC Davis as a postdoc with David Britt, where he started to work experimentally and applied high-resolution EPR spectroscopy to study the mechanisms of metalloenzymes. In 2011, he started his independent career at the University of Washington in Seattle, where he is currently Assistant Professor of Chemistry and Biophysics. He received a number of awards, among them an NSF CAREER award, the Cottrell Scholar Award and the Young Investigator Award of the International EPR Society.